Role of Red Blood Cells in Cardiovascular Disease

NCT07151222 | Recruiting

• 1 other identifier: 2024-02534
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

The risk of myocardial infarction is dependent on cardiovascular risk factors including type 2 diabetes (T2D) but underlying mechanisms are poorly understood. We identified that red blood cells (RBCs) mediate beneficial cardiovascular regulatory effects under hypoxic/ischemic conditions via signaling by nitric oxide (NO) and soluble guanylate cyclase (sGC) in the RBCs. The RBCs become dysregulated in T2D which induces endothelial and cardiac injury. This project investigates the signaling of RBCs in cardiovascular disease and explores novel therapeutic strategies that target RBC function in myocardial infarction and T2D. Aims To determine the

• mechanisms behind cardioprotective effect of RBCs in myocardial infarction
• signaling behind cardiovascular injury induced by RBCs in T2D Work plan RBCs collected from patients with myocardial infarction, patients with T2D and healthy controls are investigated in bioassays including isolated hearts of ischemia/reperfusion, endothelial function and cell cultures. Molecular mechanisms behind the effects of RBCs are identified with focus on the NO-sGC pathway in the RBCs. This project unravels the RBC as a mediator of cardiovascular disease and has the potential to identify novel therapeutic strategies by targeting RBC signaling.

Conditions

Diabetes Mellitus

Keywords

Red blood cells; Nitric oxide; diabetes

Outcome Measures

Primary Outcomes (1)

• Red blood cell function defined as their ability to modulated post-ischemic recovery of left ventricular developed pressure, myocardial infarct size and endothelium-dependent relaxation.

  The function of red blood cells (RBCs) are investigated in isolated heart preparations and in isolated aorta. The heart preparations are subjected to ischemia followed by 60 min reperfusion and RBCs are administered into the coronary circulation at the onset of ischemia. Left ventricular developed pressure is recorded as readout of left ventricular function. Final infarct size is determined at the end of the reperfusion period. Isolated arteries are co-incubated with the RBCs for 18 h. Following the incubation, the arteries are mounted in myographs for the determination of endothelium-dependent and endothelium-independent relaxations.

  At 60 min of reperfusion

Secondary Outcomes (1)

• Red blood cell production of reactive oxygen species

  At baseline and following ex vivo inhibition of ROS formation.

Study Arms (4)

Type 2 diabetes

Patients with type 2 diabetes

Type 1 diabetes

Patients with type 1 diabetes

Coronary artery disease/Myocardial infarction

Patients with acute coronary syndromes

Healthy controls

Age- and gender-matched healthy subjects

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Type 2 Diabetes

You may qualify if:

• Type 2 diabetes

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator

Study Sites (1)

Karolinska Institutet

Stockholm, Swsden, 17176, Sweden

RECRUITING

Related Publications (1)

• Pernow J, Yang J. Red blood cells: a new target to prevent cardiovascular disease? Eur Heart J. 2024 Oct 21;45(40):4249-4251. doi: 10.1093/eurheartj/ehae454. No abstract available.

  PMID: 39258963 RESULT

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• John Pernow, MD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Pernow, MD

CONTACT

+46704848361; john.pernow@ki.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: September 3, 2025
• Study Start: January 1, 2017
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2031
• Last Updated: September 3, 2025

Record last verified: 2025-08

Locations

SE (1)